Preliminary physiological experiments demonstrated a rise in tumor TpO2 using short term (10 min) localized mild hyperthermia (39-41 degree C) both in animals and humans. The mechanism of this effect conceivably could be mediated through an increase in blood flow to the cancerous tissue. Associated effects on metabolism and intercellular pH remain to be determined. We propose to measure concommitently TpO2, pH, local blood flow and tissue temperature using oxygen and pH ultramicroelectrodes (tip 1-5 micron), the local H ion generation method and microthermocouples respectively. Other functions such as blood pressure and body temperature will also be monitored. The objective is to establish the physiological mechanisms of observed rise in TpO2, as well as to document it in different tumors at several host organ sites in various species. The ratio between the increase in O2 tension in tumor and that in normal host tissue will also be studied. Simultaneous radiobiological experiments will be performed to establish if this hyperthermic tumor oxygenation can be used as an adjuvant to radiation therapy. The tumor system in the initial studies will be a transplantable mouse mammary adenocarcinoma implanted into the upper hind limb of C3H mice. A holder has been designed which will hold 4 animals simultaneously with only the tumored portion of the legs exposed. For any given radiation dose the 4 animals will be treated as follows: 1) air, no heat; 2) air, heat; 3) oxygen, no heat; 4) oxygen, heat. Each dose point will consist of a total of 10-12 animals per experimental group (i.e. 40-48 animals per dose) for each of 10 doses. The simultaneous inclusion of the 3 control groups should serve as necessary and sufficient controls. The animals will then be followed 3 x per week for both tumor and normal tissue response throughout a period of 120 days/animal (assuming cure). Based on the data obtained subsequent experiments will be performed employing an in vivo/in vitro WAG rat rhabdomyosarcoma to determine the cellular basis for the survival data obtained.